Numerous studies in mice have documented the existence of a severe age-related immunodeficiency plus a greatly increased incidence of autoimmunity. Many of the "diseases of aging" may be related to these dual manifestations of immune dysfunction. The same situation probably obtains in man. Accordingly, it is planned to study age-related immune functional parameters in normal humans up to 80 plus years of age and in a population of subjects with Down's syndrome, which may be considered as a "model" for accelerated aging. The subjects will be characterized by cytogenetic and clinical analyses. Particular immunologic focus will include: cellular immunity; suppressor and effector cells; T-cell subsets; mitogenic response; autoimmune status; immunoglobulins; HLA and B-cell alloantigens; MLC typing; neutrophil physiology; lymphocyte membrane phenomena (microtubules); lymphocyte biochemistry (cyclic nucleotides, aminoacid transport, etc.); lymphocyte DNA-excision repair efficiency. Further evidence that Down's syndrome in particular is associated with accelerated aging will be evaluated by these and other criteria. The subsequent 5-year mortality rates of the older portions of the normal and of Down's syndrome populations will be correlated with their prior immune functional status and their cytogenetic make-up.